The open-label portion of the phase 1b/2 ASIST study (NCT05322590) evaluating BXQ-350 in combination with standard of care (SOC) for first-line treatment of metastatic colorectal cancer (mCRC) has completed patient enrollment, Bexion Pharmaceuticals announced. The ASIST trial aims to assess the safety and efficacy of BXQ-350 combined with modified FOLFOX7 (mFOLFOX7) and bevacizumab (Avastin) in newly diagnosed mCRC patients, while also exploring its potential to mitigate chemotherapy-induced peripheral neuropathy (CIPN).
BXQ-350: A Novel Therapeutic Approach
BXQ-350 is a first-in-class biologic comprised of the multifunctional sphingolipid activator protein, Saposin C, and a phospholipid. Prior phase 1 trials in both adult and pediatric patients have indicated a strong safety profile and evidence of single-agent activity across a range of solid tumors. Preclinical and clinical data suggest BXQ-350 may also possess activity against chemotherapy-induced peripheral neuropathy.
ASIST Trial Design and Objectives
The ASIST trial is designed to evaluate the safety and efficacy of BXQ-350 in combination with mFOLFOX7 and bevacizumab in patients with newly diagnosed metastatic adenocarcinoma of the colon/rectum. A key objective is to determine whether BXQ-350 can reduce oxaliplatin-induced sensory neurotoxicity, potentially enabling patients to receive the full planned doses of mFOLFOX7.
Reema A. Patel, MD, associate professor of medicine at the Markey Cancer Center of the University of Kentucky, noted, "BXQ-350's mechanism of action lends itself to potential benefit in [patients with] metastatic colorectal [cancer] and peripheral neuropathy... I am excited by the potential of BXQ-350 to reduce or even potentially reverse neuropathic pain in these patients."
Patient Eligibility and Treatment Protocol
Eligible patients for the ASIST trial include those aged 18 years or older with newly diagnosed stage IV metastatic adenocarcinoma of the colon/rectum. Patients must have measurable disease at baseline per RECIST 1.1 criteria, a life expectancy of at least 3 months, and an ECOG performance status of 0 or 1. Adequate liver, renal, and bone marrow function, along with acceptable coagulation parameters, are also required.
Participants receive BXQ-350 via intravenous (IV) infusion in combination with standard doses of mFOLFOX and bevacizumab. The trial consists of two stages: an initial open-label phase to determine the appropriate dose of BXQ-350 for the subsequent blinded phase, where patients will receive either BXQ-350 or a placebo.
Endpoints and Study Completion
The primary endpoints of the ASIST trial include determining the recommended phase 2 dose, assessing the incidence of treatment-emergent adverse events using CTCAE v5.0, and measuring the objective response rate. Secondary endpoints encompass overall survival, progression-free survival, duration of response, disease control rate, peak plasma concentration, total sensory neuropathy, CIPN assessment, and post-oxaliplatin assessment. The estimated study completion date is April 2029, with enrollment ongoing at sites across multiple states.
"We are excited about advancing to the next stage of clinical development, including further discussions with FDA on study design, and we look forward to providing updates as we reach upcoming milestones in 2025," said Jim Beach, chief executive officer of Bexion.
